Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing

Cornelius H. L. Kürten, Aditi Kulkarni, Anthony R. Cillo, Patricia M. Santos, Anna K. Roble, Sayali Onkar, Carly Reeder, Stephan Lang, Xueer Chen, Umamaheswar Duvvuri, Seungwon Kim, Angen Liu, Tracy Tabib, Robert Lafyatis, Jian Feng, Shou-Jiang Gao, Tullia C. Bruno, Dario A. A. Vignali, Xinghua Lu, Riyue Bao, Lazar Vujanovic and Robert L. Ferris ()
Additional contact information
Cornelius H. L. Kürten: University Hospital Essen, University Duisburg-Essen
Aditi Kulkarni: University of Pittsburgh
Anthony R. Cillo: University of Pittsburgh
Patricia M. Santos: University of Pittsburgh
Anna K. Roble: University of Pittsburgh
Sayali Onkar: University of Pittsburgh
Carly Reeder: University of Pittsburgh
Stephan Lang: University Hospital Essen, University Duisburg-Essen
Xueer Chen: University of Pittsburgh
Umamaheswar Duvvuri: University of Pittsburgh
Seungwon Kim: University of Pittsburgh
Angen Liu: University of Pittsburgh
Tracy Tabib: University of Pittsburgh
Robert Lafyatis: University of Pittsburgh
Jian Feng: University of Pittsburgh
Shou-Jiang Gao: University of Pittsburgh
Tullia C. Bruno: University of Pittsburgh
Dario A. A. Vignali: University of Pittsburgh
Xinghua Lu: University of Pittsburgh
Riyue Bao: University of Pittsburgh
Lazar Vujanovic: University of Pittsburgh
Robert L. Ferris: University of Pittsburgh

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)+ and 12 HPV– HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV+ TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.

Date: 2021
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DOI: 10.1038/s41467-021-27619-4

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